2J1Z

Human p53 core domain mutant M133L-V203A-N239Y-N268D-F270L

Summary for 2J1Z

• Entry DOI: 10.2210/pdb2j1z/pdb
• Related: 1A1U 1AIE 1C26 1DT7 1GZH 1H26 1HS5 1JSP 1KZY 1MA3 1OLG 1OLH 1PES 1PET 1SAE 1SAF 1SAG 1SAH 1SAI 1SAJ 1SAK 1SAL 1TSR 1TUP 1UOL 1XQH 1YCQ 1YCR 1YCS 2AC0 2ADY 2AHI 2ATA 2B3G 2BIM 2BIN 2BIO 2BIP 2BIQ 2F1X 2FEJ 2J0Z 2J10 2J11 2J1W 2J1X 2J1Y 2J20 2J21 3SAK
• Descriptor: CELLULAR TUMOR ANTIGEN P53, ZINC ION (3 entities in total)
• Functional Keywords: second-site suppressor mutation, disease mutation, nuclear protein, phosphorylation, tumor suppressor, alternative splicing, li-fraumeni syndrome, li- fraumeni syndrome, host-virus interaction, transcription, metal-binding, anti-oncogene, dna-binding, transferase, polymorphism, glycoprotein, zinc, activator, apoptosis, cell cycle, acetylation, p53 dna-binding domain, transcription regulation, superstable mutant, dna-binding protein
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637
• Total number of polymer chains: 2
• Total formula weight: 49244.47

Authors

Joerger, A.C.,Fersht, A.R. (deposition date: 2006-08-15, release date: 2006-09-20, Last modification date: 2023-12-13)

Primary citation

Joerger, A.C.,Ang, H.C.,Fersht, A.R.
Structural Basis for Understanding Oncogenic P53 Mutations and Designing Rescue Drugs.
Proc.Natl.Acad.Sci.USA, 103:15056-, 2006

PubMed Abstract: The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. We have solved high-resolution crystal structures of several oncogenic mutants to investigate the structural basis of inactivation and provide information for designing drugs that may rescue inactivated mutants. We found a variety of structural consequences upon mutation: (i) the removal of an essential contact with DNA, (ii) creation of large, water-accessible crevices or hydrophobic internal cavities with no other structural changes but with a large loss of thermodynamic stability, (iii) distortion of the DNA-binding surface, and (iv) alterations to surfaces not directly involved in DNA binding but involved in domain-domain interactions on binding as a tetramer. These findings explain differences in functional properties and associated phenotypes (e.g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug.

PubMed: 17015838
DOI: 10.1073/PNAS.0607286103

Experimental method

X-RAY DIFFRACTION (1.8 Å)